Infectious disease

Cell culture and mouse studies suggest inhibiting JNK1 or its substrate AP-1 could help treat the viral infection Japanese encephalitis (JE). In JE virus-infected human glioma and murine microglial cell lines, a JNK inhibitor tool compound decreased levels of AP-1, phosphorylated JNK1 and markers of inflammation compared with vehicle. In the JE virus-infected glioma cells, siRNA targeting JNK1 or AP-1 decreased levels of TNFα, IL-1β and other inflammatory markers compared with non-specific siRNA. In mice infected with JE virus, the JNK inhibitor decreased viral load, numbers of activated microglia, neuronal cell death and other markers of viral-induced encephalitis, and brain levels of TNFα, IL-1β and other inflammatory markers, and increased survival compared with no treatment. Next steps could include testing JNK1 and AP-1 inhibitors in the infected mice.

Toyama Chemical Co. Ltd. and Roche have the AP-1 inhibitor R7277 in Phase II testing for rheumatoid arthritis...